Protein ubiquitylation is a post-translational modification (PTM) involving the covalent attachment of a small protein (ubiquitin) to specific lysine residues on target proteins. Ubiquitylation is a reversible and dynamic modification, controlled by the activities of ubiquitin ligases (E3 enzymes) and deubiquitylating enzymes (DUBs). Its roles in epigenetic regulation are recognized as contributing to gene expression, chromatin structure, and genome stability. One role of ubiquitylation in epigenetic regulation is in histone modification. Depending on the context, ubiquitylation of histones at specific lysine residues can either activate or repress gene expression. For example, monoubiquitylation of histone H2B (H2BK120ub1) is associated with transcriptional elongation. Conversely, ubiquitylation of histone H2A (H2AK119ub1) is linked to gene repression, whilst its deubiquitylation (by the USP7 DUB) is important for maintaining an open chromatin state and gene expression. USP7 can also directly regulate the expression of DDR genes by modulating the chromatin structure at their promoter regions. By removing this ubiquitin mark, USP7 promotes an open chromatin state at the promoters of DDR genes, allowing for efficient repair processes. Another important aspect of epigenetic regulation mediated by ubiquitylation involves DNA methylation. DNA methyltransferases, which add methyl groups to DNA, are themselves subjected to ubiquitylation. Ubiquitylation of DNA methyltransferases can regulate their stability and activity, thus influencing DNA methylation patterns and ultimately gene expression. Ubiquitylation also plays a role in maintaining genome stability by directly regulating proteins involved in the DNA damage response (DDR). When DNA is damaged, various proteins involved in DDR are ubiquitylated to coordinate repair processes. For example, BRCA1 is involved in various DDR pathways and is subjected to ubiquitylation by the E3 ubiquitin ligase RAP80-BRCC36 complex which helps recruit BRCA1 to DNA damage sites, facilitating homologous recombination repair. Moreover, ubiquitylation is involved in the regulation of epigenetic writers and erasers. For instance, E3 ubiquitin ligases can target histone modifiers for degradation, affecting the balance of histone acetylation and methylation, thereby influencing gene expression patterns. Additionally, DUBs can remove ubiquitin moieties from epigenetic regulators, regulating their activities and modulating chromatin structure. For example, USP7 interacts with and stabilizes the p300/CBP family of HATs, involved in histone acetylation and transcriptional regulation. Finally, ubiquitylation also plays a role in regulating transcription factors. Ubiquitylation can control the stability, activity, and subcellular localization of many transcription factors, thereby influencing their ability to bind to specific genomic regions and regulate gene expression. For example, Forkhead box O (FOXO) transcription factors regulate stress responses and are themselves regulated by ubiquitylation. The E3 ubiquitin ligase MDM2 can ubiquitylate and inhibit FOXO proteins by promoting their cytoplasmic localization. Conversely, under stress conditions, FOXO proteins escape ubiquitylation, allowing them to translocate to the nucleus and activate target genes. Thus, protein ubiquitylation is a fundamental PTM with multifaceted roles in epigenetic regulation, influencing chromatin structure, histone modifications, DNA methylation, and the stability and activity of epigenetic and transcriptional regulators. We offer a comprehensive product catalogue of research reagents for investigating protein ubiquitylation, including BRCA1 antibodies, Ubiquitin antibodies, Nrf2 antibodies, Ubiquitin ELISA Kits, and Keap1 ELISA Kits. Explore our full protein ubiquitylation product range below and discover more, for less.